Samples and data are analyzed from a longitudinal population study conducted from 1965 to 2007 that allows study of the risk factors and effects of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on development of vascular complications and mortality. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. These findings are reported in DK069028 (Genetic epidemiology of diabetes and obesity) and DK069094 (Genetic epidemiology of diabetic complications). A genome-wide association study implicated variants in the DNER gene in susceptibility to type 2 diabetes. Patterns of DNA methylation (an epigenetic mark) in blood cells were associations with past exposure to diabetes in utero, a strong risk factor for diabetes, suggesting a mechanism for the effect of this risk factor. A variant in the gene ABCC8 is associated with increased risk of type 2 diabetes. One study participant who was discovered to be homozygous for the variant had a history of hyperinsulinemic hypoglycemia of infancy, consistent with reports from elsewhere of other variants in this gene causing this condition. Variants in several other genes were associated with diabetes or obesity in this population. Knowledge of diabetes risk factors coming from this and other studies led to the hypothesis that type 2 diabetes could be prevented or delayed in adults at high short-term risk. This hypothesis was confirmed in the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial in which many of the participants and investigators in this project participated. We are now in a long-term follow-up phase, the Diabetes Prevention Program Outcomes Study (DPPOS), to assess long-term success with weight loss, reduction in the incidence of diabetes, and effects on diabetes complications. This study is reported in DK075078 (Prevention of type 2 diabetes). Other findings related to kidney complications of diabetes are reported in DK069062 (Epidemiology, pathophysiology and treatment of diabetic nephropathy). &#8195;